Research Paves Way for Novel Therapy to Treat Osteoporosis, Atherosclerosis

By Amy Widner

June 27, 2018 | June 27, 2018 | A recent study by University of Arkansas for Medical Sciences (UAMS) and Central Arkansas Veterans Healthcare System (CAVHS) researchers shows that a type of blood protein we are all born with protects against osteoporosis, illuminating the potential for a novel approach to treatment.

Ambrogini used a genetically modified mouse developed at the University of California San Diego (UCSD), where researchers conducted a related study that showed this protein also has a beneficial effect on cardiovascular disease, specifically atherosclerosis, in which plaque builds up inside the arteries.

“Together, the two studies provide proof of principle for a new therapy for two very common diseases, osteoporosis and atherosclerosis, simultaneously,” Ambrogini said. “In the case of osteoporosis, this would be a new anabolic therapy, meaning that it can build new bone as opposed to only preventing the loss of old bone.”

Everyone is born with innate immune antibodies that help fight bacteria and other pathogens. The study found that these antibodies protect against bone loss induced by a high-fat diet. Importantly, the UAMS researchers found that even in the absence of a high-fat diet, the levels of these antibodies decrease as mice grow older, which may contribute to age-related bone loss. By giving back these antibodies, Ambrogini was able stop the bone loss in the mice and build new bone.

Meanwhile, the UCSD researchers found that the same antibodies strongly protect against atherosclerosis and cardiovascular disease.

Robert L. Jilka, Ph.D., a co-author on the study and professor of medicine, has been studying the relationship between atherosclerosis and osteoporosis for about 10 years.

“We have known for quite some time that there was some sort of connection between osteoporosis, atherosclerosis and the high-fat diet,” Jilka said. “Investigators all over the world have been studying this for a while without much success as to the reason for this connection.”

This groundbreaking finding is the latest in 24 years of significant advances in the understanding of osteoporosis and other bone diseases because of research conducted at the Center for Osteoporosis and Metabolic Bone Diseases at UAMS and CAVHS.

The center is one of the largest and longest-funded osteoporosis research centers in the world. It is directed by Stavros Manolagas, M.D., Ph.D., a distinguished professor of medicine, professor of orthopaedics, director of the Division of Endocrinology and Metabolism and co-author on Ambrogini’s publication.

The UAMS Center for Musculoskeletal Disease Research also provided support. The center, directed by Professor Charles O’Brien, Ph.D., is funded by $11.3 million in federal funds over five years from an NIH Centers of Biomedical Research Excellence (COBRE) grant. The grant supports junior researchers like Ambrogini as they work to secure their own independent funding and establish their careers.

“It would not have been possible for Dr. Ambrogini to do this work in a vacuum,” said Vice Chancellor for Research Lawrence Cornett, Ph.D. “The work of Dr. Manolagas, Dr. O’Brien and Dr. Jilka, along with the vast assembly of knowledge and talent found among the scientists and support staff in the two bone research centers, was essential. This is yet another illustration of the importance of team science and long-term, consistent support for research.”

Ambrogini came to UAMS in 2007 from Italy after she completed her medical degree and specialization in endocrinology at the University of Pisa. She conducted research at the Center for Osteoporosis while working on her Ph.D. degree. She stayed at UAMS for a residency in internal medicine and a fellowship in endocrinology and metabolism. She joined the endocrinology faculty three years ago.

“I couldn’t be more pleased,” Ambrogini said. “This publication comes at a perfect time for my career development. I’m excited and look forward to the translation of this science into a treatment for these conditions, which affect so many of my patients.”

UAMS is the state's only health sciences university, with colleges of Medicine, Nursing, Pharmacy, Health Professions and Public Health; a graduate school; hospital; a main campus in Little Rock; a Northwest Arkansas regional campus in Fayetteville; a statewide network of regional campuses; and seven institutes: the Winthrop P. Rockefeller Cancer Institute, Jackson T. Stephens Spine & Neurosciences Institute, Harvey & Bernice Jones Eye Institute, Psychiatric Research Institute, Donald W. Reynolds Institute on Aging, Translational Research Institute and Institute for Digital Health & Innovation. It is the only adult Level 1 trauma center in the state. UAMS has 2,727 students, 870 medical residents and five dental residents. It is the state's largest public employer with more than 10,000 employees, including 1,200 physicians who provide care to patients at UAMS, its regional campuses, Arkansas Childrens Hospital, the VA Medical Center and Baptist Health. Visit www.uams.edu or www.uamshealth.com. Find us on Facebook, Twitter, YouTube or Instagram.